Testing a new oral polio vaccine in Bangladesh

A Phase 2, Randomized, Observer-blind, Controlled, Age De-escalation, Dosage Escalation Study to Assess Safety and Immunogenicity of a Novel Live Attenuated Type 1 Oral Poliomyelitis Vaccine in Healthy Young Children, Infants, and Neonates in Bangladesh

This study is testing a new oral polio vaccine in young children in Bangladesh to see if it works better and has fewer side effects than the current vaccine.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 2232 (estimated)
• Ages: 0 Days to 4 Years
• Sex: All
• Sponsor: Path (Academic / other)
• Locations: 1 site (Dhaka)
• Trial ID: NCT05644184 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, tolerability, and immunogenicity of a novel oral poliomyelitis vaccine (nOPV1) compared to the existing Sabin monovalent type 1 vaccine (mOPV1) in a pediatric population. The study involves 192 healthy young children, 720 infants, and 1100 neonates, who will receive varying doses of nOPV1 or the control vaccine. Participants will be monitored for vaccine response and potential side effects over a period of up to 32 weeks. The trial aims to assess the vaccine's ability to reduce fecal shedding of the virus after a challenge with the Sabin strain.

Who should consider this trial

Good fit: Ideal candidates include healthy infants and children aged 1 day to less than 5 years who have completed their routine polio immunization.

Not a fit: Patients with significant medical conditions or congenital anomalies may not benefit from this study.

Why it matters

Potential benefit: If successful, this vaccine could provide a safer and more effective means of preventing poliomyelitis in young children.

How similar studies have performed: Other studies have shown promise with similar vaccine approaches, but this specific trial is novel in its assessment of nOPV1.

Eligibility criteria

Inclusion Criteria for all participants:

1. Healthy, as defined by the absence of any clinically significant medical condition or congenital anomaly as determined by medical history, physical examination, and clinical assessment of the investigator
2. Parent(s) or guardian(s) willing and able to provide written informed consent prior to performance of any study-specific procedure
3. Resides in study area and parent understands and is able and willing to adhere to all study visits and procedures (as evidenced by a signed informed consent form \[ICF\] and assessment by the investigator)
4. Parent agrees for participant to receive all routine infant and childhood immunizations as per the approved protocol-adjusted schedule

Inclusion Criteria for Cohort 1 (young children) participants only:

1. Male or female child from 1 to less than 5 years of age at the time of initial study vaccination
2. Based on documentation, previously received a 3 or 4 dose primary poliomyelitis immunization series containing OPV (may have also received IPV), with last dose received more than 3 months prior to initial study vaccination

Inclusion Criteria for Cohort 2 (infants) participants only:

1. Male or female infant expected to be 6 weeks of age (43rd to 49th day of life \[with day of birth being the first day of life\], inclusive+ 6-day window), at the time of initial study vaccination
2. Prior to study vaccination has received no doses of IPV or OPV, based on no evidence of such vaccination per available documentation.

Inclusion Criteria for Cohort 3 (neonates) participants only:

1. Male or female newborn (1st day of life+ 3-day window, inclusive), at the time of initial study vaccination
2. Prior to study vaccination has received no doses of IPV or OPV or rotavirus vaccine, based on no evidence of such vaccination per available documentation.

Exclusion Criteria for all participants:

1. For all participants, the presence of anyone under 10 years of age in the participant's household (living in the same house or apartment unit) who does not have complete "age appropriate" vaccination status with respect to poliovirus vaccines at the time of study vaccine administration. For household members younger than 10 years of age, "age appropriate" vaccination is complete series of trivalent Oral Poliovirus Vaccine (tOPV) or at least three doses of bivalent (types 1 and 3) Oral Poliovirus Vaccine (bOPV) plus a booster fractional dose of IPV (fractional dose Inactivated Polio Vaccine; fIPV). Note: A vaccination series of tOPV or at least three doses of bOPV with our without a booster fractional dose of IPV will be considered sufficient.
2. For all participants, having a member of the participant's household (living in the same house or apartment unit) who has received OPV based on the vaccination records in the previous 3 months before study vaccine administration.
3. Any participating children attending day care or pre-school during their participation in the study until one month after their last study vaccine administration.
4. Moderate or severe (grade ≥ 2) acute illness at the time of enrollment/first study vaccination - temporary exclusion. Participant with mild (grade 1) acute illnesses may be enrolled at the discretion of the investigator.
5. Presence of fever on the day of enrollment/first study vaccination (axillary temperature ≥37.5˚C) - (Temporary exclusion for Cohorts 1 and 2)
6. A known allergy, hypersensitivity, or intolerance to any components of the study vaccines, including all macrolide and aminoglycoside antibiotics (e.g., erythromycin and kanamycin)
7. Evidence of a clinically significant congenital or genetic defect as judged by the investigator
8. History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids (\> 0.5mg/kg/day of prednisolone (or equivalent)). Topical and inhaler steroids are permitted (unless indicative of a significant chronic illness otherwise excluding the infant/young child)
9. Any self-reported known or suspected immunosuppressive or immunodeficiency condition (including HIV infection) in the participant or household member (living under the same roof/in the same building rather than in the same compound)
10. Receipt of any immune-modifying or immunosuppressant drugs within 6 months prior to the first study vaccine dose or planned use during the study of study participants or a household member
11. Any known or suspected bleeding disorder in the participant that would pose a risk to venipuncture or intramuscular injection
12. Presence of sever malnutrition \[weight-for-length/height z-score greater than or equal to -3 SD median (per WHO published growth standards)\] - temporary exclusion if marginal and subsequently gains weight.
13. Participation in another investigational product (drug or vaccine) clinical trial within 30 days prior to entry in this study or receipt of any such investigational product other than the study vaccine within 30 days prior tot he first administration of study vaccine, or planned use during the study period.
14. Receipt of transfusion of any blood product or immunoglobulins within 12 months prior to the first administration of study vaccine or planned use during the study period.
15. Parent or participant has any condition that in the opinion of the investigator would increase the participant's health risks in the study participation or would increase the risk of not achieving the study's objectives (e.g., would compromise adherence to protocol requirements or interfere with planned safety and immunogenicity assessments.)

Exclusion Criteria for Cohort 2 \& 3 participants only:

1. Low birth weight (LBW) in newborn participants which is defined as a birth weight of less than 2500g (up to and including 2499b) at the time of birth or by the time of enrolment.
2. Premature birth (less than 37 weeks gestation)
3. From multiple birth (due to increased risk of OPV transmission between siblings)

Where this trial is running

Dhaka

• International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) — Dhaka, Bangladesh (Recruiting)

Study contacts

• Principal investigator: K. Zaman, MBBS, MPH, PhD, FRCP — International Centre for Diarrhoeal Disease Research, Bangladesh
• Study coordinator: Tushar Tewari, MD

Conditions Poliomyelitis; Vaccine tolerability; Vaccine safety; Vaccine reactogenicity; Vaccine viral shedding; Vaccine immunogenicity